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| [[Image:1hwg.gif|left|200px]] | | [[Image:1hwg.png|left|200px]] |
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| ==Overview==
| | {{ABSTRACT_8943276}} |
| Human growth hormone binds two receptor molecules and thereby induces signal transduction through receptor dimerization. At high concentrations, growth hormone acts as an antagonist because of a large difference in affinities at the respective binding sites. This antagonist action can be enhanced further by reducing binding in the low affinity binding site. A growth hormone antagonist mutant Gly-120 --> Arg, has been crystallized with its receptor as a 1:1 complex and the crystal structure determined at 2.9 A resolution. The 1:1 complex is remarkably similar to the native growth hormone-receptor 1:2 complex. A comparison between the two structures reveals only minimal differences in the conformations of the hormone or its receptor in the two complexes, including the angle between the two immunoglobulin-like domains of the receptor. Further, two symmetry-related 1:1 complexes in the crystal form a 2:2 complex with a large solvent inaccessible area between two receptor molecules. In addition, we present here a native human growth hormone-human growth hormone-binding protein 1:2 complex structure at 2.5 A resolution. One important difference between our structure and the previously published crystal structure at 2.8 A is revealed. Trp-104 in the receptor, a key residue in the hormone-receptor interaction, has an altered conformation in the low affinity site enabling a favorable hydrogen bond to be formed with Asp-116 of the hormone.
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| ==About this Structure== | | ==About this Structure== |
| 1HWG is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The following page contains interesting information on the relation of 1HWG with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb52_1.html Growth Hormone]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HWG OCA]. | | 1HWG is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The following page contains interesting information on the relation of 1HWG with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb52_1.html Growth Hormone]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HWG OCA]. |
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| ==Reference==
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| Crystal structure of an antagonist mutant of human growth hormone, G120R, in complex with its receptor at 2.9 A resolution., Sundstrom M, Lundqvist T, Rodin J, Giebel LB, Milligan D, Norstedt G, J Biol Chem. 1996 Dec 13;271(50):32197-203. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8943276 8943276]
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| [[Category: Growth Hormone]] | | [[Category: Growth Hormone]] |
| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
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| [[Category: Hormone]] | | [[Category: Hormone]] |
| [[Category: Receptor]] | | [[Category: Receptor]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 19:17:45 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jun 26 17:30:39 2008'' |
